Integrins are heterodimeric matrix receptors that anchor cells to substrates and transmit externally derived signals across the plasma membrane. Integrin αvβ3 is a type of integrin that is a receptor for vitronectin. Integrin αvβ3 is expressed at low levels in most normal cells including intestinal, vascular, and smooth muscle cells. The cell types that express high levels of this heterodimer molecular include bone-resorbing osteoclasts, activated macrophages, a small fraction of neutrophils, angiogenic endothelial cells and migrating smooth muscle cells. Integrin αvβ3 is involved in the osteoclast-mediated bone resorption, both in vivo and in vitro, as well as new blood vessel formation. This heterodimer molecule recognizes the amino acid motif Arg-Gly-Asp (RGD) contained in bone matrix proteins such as osteopontin and bone sialoprotein.
Disintegrins are a family of low-molecular-weight RGD-containing peptides that bind specifically to integrins αIIbβ3, α5β1 and αvβ3 expressed on platelets and other cells including vascular endothelial cells and some tumor cells.
Various disintegrins are known in the art, including rhodostomin and its variants, including but not limited to ARLDDL.
Angiogenesis-related eye diseases are eye diseases which are related to the growth of new blood vessels from pre-existing vessels. These diseases include but are not limited to, age-related macular degeneration, diabetic retinopathy, corneal neovascularizing diseases, retinal angiomatous proliferation, polypoidal choroidal vasculopathy, ischaemia-induced neovascularizing retinopathy, high myopia and retinopathy of prematurity.
Because existing drugs are not satisfactorily effective in the treatment of angiogenesis-related eye diseases, there is a need for novel treatments of these diseases.